The liver first pass effects and bile concentrations of (-)-, (+)- and (+/-)-praziquantel in rabbits

Praziquantel (PQT) is a racemic mixture. Intragastric gavage of (-)-, (+)- and (+/-)-PQT 100 mg/kg were used to study the liver first pass effects in rabbits. HPLC was used to determine the concentration of each compound in the portal and systemic circulation, and in the bile within 4h. The results showed that all drugs were absorbed rapidly from the gut into the portal vein. The serum concentration in the portal vein were similar. However, over 90% of PQT and its enantiomers were extracted in the first passage through the liver. Intrinsic metabolic clearances of the liver of (-)-, (+)- and (+/-)-PQT were 50.3, 174.4 and 52.6 L/h, respectively. The serum concentrations of the three drugs markedly decreased in the systemic circulation, especially that of (+)-PQT. The AUC of (+)-PQT was apparently lower than that of (-)- or (+/-)-PQT. From these results, it is assumed that the first pass effects of PQT and its enantiomers in the liver are pronounced and most likely stereoselective. Also, unchanged PQT and its enantiomers were found in the bile of the rabbits.     

乳母血清泌乳素水平与泌乳量关系的观察

用放射免疫法测定产后40天和60天乳母血清泌乳素基础水平和吸吮后泌乳素最大反应性增值,发现其与乳母泌乳量、婴儿吸吮频率、吸吮时间之间均不存在正相关关系,推测引起泌乳素分泌除吸吮外,还存在其他机理。     

Objective responses in patients with malignant melanoma or renal cell cancer in early clinical studies do not predict regulatory approval.

PURPOSE: Tumor responses in early-phase trials are used to determine whether new agents warrant further study. Given that spontaneous regressions are observed in melanoma and renal cell carcinoma, this study assessed whether tumor responses, particularly in these two tumor types, predict for future regulatory drug approval. EXPERIMENTAL DESIGN: The literature was reviewed to assess tumor response rates to cytotoxic agents in phase I and II trials in the following solid tumors: melanoma, renal cell carcinoma, non-small-cell lung cancer, breast cancer, ovarian cancer, colorectal cancer, and other solid tumors. Response rates were categorized and the relationship of these categories to the end point of regulatory drug approval was determined. RESULTS: Fifty-eight drugs were assessed in 100 phase I trials, and 46 of these drugs were also studied in 499 phase II trials. Higher overall response rates in both phase I trials (P = 0.03) and phase II trials (P < 0.0001) were predictive of regulatory approval. However, response in melanoma or renal cell carcinoma was not predictive for either phase I or phase II studies. CONCLUSIONS: For cytotoxic agents, although overall objective response rates reliably predict subsequent marketing approval, isolated responses in melanoma and renal cell carcinoma are not predictive.     

外周血细胞DNA、RNA及血红蛋白同时提取法

采用淋巴细胞分离液分离外周血中的有核细胞。经细胞裂解液处理，上清提取RNA，沉淀提取DNA，用分离液分离所得红细胞沉淀制备血红蛋白溶液，经对抽提物质量进行评价，发现3种提取物质量均高，本法能从少量外周血中同时分离DNA、RNA及血红蛋白，高效易操作，值得推广。     

Mechanisms of immunotherapeutic intervention by anti-CD154 (CD40L) antibody in high-risk corneal transplantation.

This study aimed to determine the effects of anti-CD154 on T cell cytokine profiles and ocular chemokine gene expression after high-risk corneal transplantation and to specifically determine if CD154 blockade is associated with a switch from a Th1 to a Th2 alloimmune response. Mice were used as recipients of syngeneic or multiple minor H or MHC antigen-mismatched corneal grafts. Recipient beds were neovascularized (high-risk). Hosts were randomized to receive either anti-CD154 antibody or control immunoglobulin (Ig) perioperatively. Two weeks after corneal transplantation, allospecific delayed-type hypersensitivity (DTH) was evaluated. Frequencies of interferon-gamma (IFN-gamma)-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in the hosts were measured by enzyme-linked immunospot (ELISPOT) assay. Ocular chemokine gene expression in anti-CD154-treated and control hamster Ig-treated groups was determined using a multiprobe ribonuclease protection assay (RPA). Leukocyte infiltration of corneal grafts was evaluated microscopically. Anti-CD154-treated mice did not exhibit allospecific DTH. The frequencies of Th1 cytokine-producing but not Th2 cytokine-producing T cells were significantly reduced in anti-CD154-treated hosts. Postoperative mRNA levels of RANTES and macrophage inflammatory protein-1beta (MIP-1beta) in anti-CD154-treated eyes were substantially suppressed compared with hamster Ig-treated controls. Leukocyte infiltration was profoundly suppressed in grafts of anti-CD154-treated hosts. These data demonstrate that blockade of the CD40-CD154 costimulatory pathway after corneal transplantation inhibits Th1-mediated responses but does not induce a switch to a Th2-specific response. In addition, anti-CD154 therapy suppresses ocular chemokine gene expression and leukocytic infiltration into allografts.     

糖尿病肾脏胶原非酶糖化与氨基胍阿斯匹林的治疗作用

本实验系统观察了ＳＴＺ所致糖尿病鼠在１、３、６个月后肾脏组织胶原发生非酶糖化的情况，及氨基胍、阿斯匹林对肾脏胶原非酶糖化的阻断作用。结果表明：各病程糖尿病动物肾组织的胶原含量和非酶糖化早期产物（５－ＨＭＦ）及胶原相联荧光值均明显高于正常对照。氨基胍能够减弱糖尿病动物肾组织胶原含量的增加和荧光产物的生成，但对５－ＨＭＦ含量无影响。阿斯匹林未显示出对胶原非酶糖化的影响。     

引导科技干部保持医院发展转型期间和谐心态的着力点

当前部队医院正处于发展转型期，如何引导科技干部适应转型发展新形势，经受住各种考验，始终保持理性平和、协调平衡、积极向上的心理状态，是一个不容忽视的现实问题，也是事关医院内部和谐和医院建设发展又好又快的大事，更是我们思想政治工作者必须着力认真研究、加以解决的重要课题。     

Computation of Time-Constant Histograms from the Forced Expired Volume-Time Curves

An efficient BASIC program was established on Apple-Ⅱmicrocomputer with the CHESTAC-35F pulmonary function testing system tocalculate the time-constant histogram from the spirogram.By a set of analogousstudies,we confirmed that the recovered time-constant histogram was within onecompartment of the assumed one and that the root of mean square values of theresiduals between the experimental and model volume-time curves was 0.02.Infour healthy adult subjects,the mean value of time-constant histograms(TCx)hadthe variation coefficient 6.6％.The results show that our method is reliable andreproducible,and it can be used for clinical investigation.     

中医脊柱手法与西医手法的对比研究

东西方在脊柱手法方面都有很多研究，近年来研究进展迅速，取得了一些进步，为临床治疗因脊柱原因引起的痛症提供了一种新的有效方法。在西方手法医学的基础上，认真研究短杠杆微调手法，对颈椎、腰椎手法进行改进，通过临床实践，手法实用效果良好。     

颞部-颌下联合进路切除咽旁颞下区巨大肿瘤(附2例报道)

[目的]探讨切除侵犯中颅窝的咽旁颞下区巨大肿瘤安全而彻底的手术进路.利用颞部切口可充分暴露中颅窝底和颞下窝以及颌下进路显露咽旁区解剖的特点,联合进路切除2例咽旁颞下区巨大肿瘤.2例侵犯中颅窝底的咽旁颞下区肿瘤顺利切除,患者术中组织损伤、出血量相对较少,术后无严重并发症.[结论]颞部-颌下联合进路适合于侵犯中颅窝底的咽旁颞下区肿瘤的手术切除.